5217

PFN2

We investigated the role of profilin 2 in the stemness, migration, and invasion of HT29 cancer stem cells (CSCs). Increased and decreased levels of profilin 2 significantly enhanced and suppressed the self-renewal, migration, and invasion ability of HT29 CSCs, respectively. Moreover, profilin 2 directly regulated the expression of stemness markers (CD133, SOX2, and beta-catenin) and epithelial mesenchymal transition (EMT) markers (E-cadherin and snail). CD133 and beta-catenin were up-regulated by overexpression of profilin 2 and down-regulated by depletion of profilin 2. SOX2 was decreased by profilin 2 depletion. E-cadherin was not influenced by profilin 2- overexpression but increased by profilin 2- knockdown. The expression of snail was suppressed by profilin 2- knockdown. We speculated that stemness and the EMT are closely linked through profilin 2-related pathways. Therefore, this study indicates that profilin 2 affects the metastatic potential and stemness of colorectal CSCs by regulating EMT- and stemness-related proteins.

PFN2 is an invasion promoter in several cancers including lung cancer. However, the probable effects and underlying mechanisms of PFN2 in tumor cell epithelial-mesenchymal-transition (EMT) of non-small cell lung cancer (NSCLC) remain poorly understood. The protein and mRNA levels of PFN2 in human bronchial epithelial cell line 16HBE and three NSCLC cell lines A549, NCI-H520 and 95D were assessed. The gain-of-function (overexpression) and lossof-function (siRNA) experiments of PFN2 were performed in 95D cells. A dual-luciferase reporter assay, western blotting and real-time PCR were used to investigate the relationship between PFN2 and miR30a5p. PFN2 was upregulated in three NSCLC cell lines, and the highest in 95D cell line. Furthermore, the upregulation of PFN2 promoted, whereas the downregulation of PFN2 suppressed invasion and EMT in 95D. Dual-luciferase reporter assay showed that miR30a5p directly interacts with the 3'-untranslated region (3'-UTR) of PFN2 mRNA. Interestingly, miR30a5p negatively regulates the expression of PFN2 and suppresses EMT and invasion in 95D. In summary, the present study demonstrated that miR30a5p inhibits EMT and invasion in high invasive NSCLC cell lines via targeting PFN2. Suggesting the association of miR30a5p and PFN2 may play an essential role in the development of NSCLC by modulating EMT and cell invasion.